What are the alternatives to Lubiprostone (cyclopropane heptanoic acid, gamma-lactone) for treating constipation?

Alternatives to Lubiprostone for Treating Constipation

Linaclotide is the most effective alternative to lubiprostone for treating constipation, particularly for irritable bowel syndrome with constipation (IBS-C), with high-quality evidence supporting its efficacy and safety profile. 1

First-Line Alternatives

Guanylate Cyclase-C Agonists

• Linaclotide

  • Strongest recommendation with high-quality evidence for IBS-C 1
  • Dosage: Standard dosing for adults with chronic idiopathic constipation
  • Efficacy: Shows modest beneficial effects with combined improvement in abdominal pain and increase in complete spontaneous bowel movements 1
  • Side effects: Diarrhea is common but discontinuation rates are low 1

• Plecanatide

  • Another guanylate cyclase-C agonist effective for IBS-C 1
  • Side effect profile similar to linaclotide with diarrhea being common 1
  • Less available in many countries outside the USA

Sodium-Hydrogen Exchange Inhibitors

• Tenapanor
  • Strong recommendation with high-quality evidence 1
  • Efficacious second-line drug for IBS-C
  • Common side effect: diarrhea
  • May not be available in many countries outside the USA

Other Pharmacological Options

5-Hydroxytryptamine 4 Receptor Agonists

• Tegaserod
  • Strong recommendation with moderate-quality evidence 1
  • Effective for IBS-C but limited availability (USA only)
  • Side effect: diarrhea is common

For Opioid-Induced Constipation

• Peripherally acting μ-opioid receptor antagonists
  • Can be used in combination therapy for enhanced efficacy in opioid-induced constipation 2
  • Examples include methylnaltrexone

Dosing Considerations

When switching from lubiprostone to alternatives, consider the following dosing guidelines:

• Linaclotide: Standard dosing for adults with chronic idiopathic constipation
• For IBS-C patients: Lower doses may be appropriate (similar to how lubiprostone uses 8 mcg twice daily for IBS-C versus 24 mcg twice daily for chronic constipation) 2, 3

Clinical Decision Algorithm

1. For patients with IBS-C:

   • First choice: Linaclotide (strongest evidence) 1
   • Alternative options: Plecanatide or tenapanor if available 1

2. For patients with chronic idiopathic constipation:

   • Linaclotide (high-quality evidence) 1
   • Tenapanor (if available) 1

3. For patients with opioid-induced constipation:

   • Consider peripherally acting μ-opioid receptor antagonists 2

Important Clinical Considerations

• Monitor for diarrhea with all secretagogues, especially with linaclotide, plecanatide, and tenapanor 1
• Patients who prioritize avoiding diarrhea may prefer alternatives with lower rates of this side effect 1
• Cost considerations are important as these medications may have higher out-of-pocket expenses 1
• Effects of secretagogues like linaclotide generally manifest within days in responders 2
• Periodically reassess the need for continued therapy to ensure optimal treatment management 2

Common Pitfalls to Avoid

• Failing to warn patients about potential side effects, particularly diarrhea with linaclotide and other secretagogues
• Not considering medication costs and insurance coverage when selecting alternatives
• Overlooking the need for dose adjustments when switching between medications for different constipation subtypes
• Not reassessing treatment efficacy after initiation of therapy